Recent studies have demonstrated that metabolites from bacterial species within the genus Streptomyces cause dopamine neurodegeneration in the nematode model organism C. elegans and in human SH-SY5Y neuroblastoma cells. These bacteria are common in soil environments and exposure to their excretions may be a missing component toward explaining why Parkinson disease (PD) is more prevalent in individuals with a rural lifestyle. While exposure to pesticides may be partially responsible for PD in rural areas, the odds ratio for farming itself cannot be accounted for by pesticide exposure alone. This R15 AREA grant proposal will allow us to purify, characterize, and chemically synthesize the bacterial neurodegenerative metabolite and examine soils to determine the prevalence of producing streptomycete strains. Because the state of Alabama exhibits a high diversity of soil types (due largely to the convergence of 4 geographic provinces) and land use patterns, it provides an ideal location in which to conduct this research. Streptomyces spp. isolates will be cultivated from the various soils for analysis of dopamine neurodegeneration in C. elegans. In total, 2000 Streptomyces isolates will be screened during this project. Additionally, this project will provide hands-on research training for at least 2 graduate students and a large number of undergraduate researchers. The University of Alabama is a learner-centered institution and promotes the inclusion of undergraduates in research opportunities. PUBLIC HEALTH RELEVANCE: Although the cause of most Parkinson Disease (PD) is unknown, it is the second most prevalent neurodegenerative disorder. Recent studies have shown that some soil bacteria produce metabolites that cause neurodegeneration in both nematode worms and a human nerve cell line. Because a rural lifestyle was implicated as a risk factor for PD, this project will determine if bacterial sources of exposure have the potential to contribute to the development of PD.